DE4141928A1 - Neue phosphonobernsteinsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel - Google Patents
Neue phosphonobernsteinsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittelInfo
- Publication number
- DE4141928A1 DE4141928A1 DE4141928A DE4141928A DE4141928A1 DE 4141928 A1 DE4141928 A1 DE 4141928A1 DE 4141928 A DE4141928 A DE 4141928A DE 4141928 A DE4141928 A DE 4141928A DE 4141928 A1 DE4141928 A1 DE 4141928A1
- Authority
- DE
- Germany
- Prior art keywords
- general formula
- acid
- alk
- compounds
- lower alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 77
- 238000000034 method Methods 0.000 title claims abstract description 16
- -1 PHOSPHON AMBER ACID DERIVATIVES Chemical class 0.000 title claims description 38
- 229940126601 medicinal product Drugs 0.000 title description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 8
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 5
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 125000003277 amino group Chemical group 0.000 claims abstract description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims abstract description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000011575 calcium Substances 0.000 claims abstract description 3
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract 3
- 239000003814 drug Substances 0.000 claims abstract 2
- 239000002253 acid Substances 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
- 150000007513 acids Chemical class 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- XUYJLQHKOGNDPB-UHFFFAOYSA-N carboxymethyl phosphonic acid Natural products OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 claims description 4
- KMDMOMDSEVTJTI-UHFFFAOYSA-N 2-phosphonobutanedioic acid Chemical class OC(=O)CC(C(O)=O)P(O)(O)=O KMDMOMDSEVTJTI-UHFFFAOYSA-N 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 3
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims description 2
- 239000012050 conventional carrier Substances 0.000 claims 1
- 208000030159 metabolic disease Diseases 0.000 claims 1
- 125000006193 alkinyl group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 230000002503 metabolic effect Effects 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 49
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 4
- 229910000105 potassium hydride Inorganic materials 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- GETQZCLCWQTVFV-UHFFFAOYSA-N anhydrous trimethylamine Natural products CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 150000001733 carboxylic acid esters Chemical class 0.000 description 3
- 229920001429 chelating resin Polymers 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 238000006845 Michael addition reaction Methods 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000000746 allylic group Chemical group 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- PWLNAUNEAKQYLH-UHFFFAOYSA-N butyric acid octyl ester Natural products CCCCCCCCOC(=O)CCC PWLNAUNEAKQYLH-UHFFFAOYSA-N 0.000 description 2
- 125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 229920006158 high molecular weight polymer Polymers 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- UUIQMZJEGPQKFD-UHFFFAOYSA-N n-butyric acid methyl ester Natural products CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 150000003459 sulfonic acid esters Chemical class 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 125000004825 2,2-dimethylpropylene group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[*:1])C([H])([H])[*:2] 0.000 description 1
- DWIKYFWVCREMNE-UHFFFAOYSA-N 2-(2-aminoethyl)-3-phosphonobutanedioic acid Chemical compound NCCC(C(O)=O)C(C(O)=O)P(O)(O)=O DWIKYFWVCREMNE-UHFFFAOYSA-N 0.000 description 1
- FKTGRGBNJODZMK-UHFFFAOYSA-N 2-(4-imidazol-1-ylbutyl)-3-phosphonobutanedioic acid Chemical compound OC(=O)C(P(O)(O)=O)C(C(=O)O)CCCCN1C=CN=C1 FKTGRGBNJODZMK-UHFFFAOYSA-N 0.000 description 1
- KVYYZLJNURMSPK-UHFFFAOYSA-N 2-(5-amino-2-methylpentyl)-3-phosphonobutanedioic acid Chemical compound NCCCC(C)CC(C(C(O)=O)P(O)(O)=O)C(O)=O KVYYZLJNURMSPK-UHFFFAOYSA-N 0.000 description 1
- SXFGJATXHINJKW-UHFFFAOYSA-N 2-(imidazol-1-ylmethyl)-3-phosphonobutanedioic acid Chemical compound OC(=O)C(P(O)(O)=O)C(C(=O)O)CN1C=CN=C1 SXFGJATXHINJKW-UHFFFAOYSA-N 0.000 description 1
- MHDLIUDYLQIASP-UHFFFAOYSA-N 2-[methyl(prop-2-ynyl)amino]-3-phosphonobutanedioic acid Chemical compound C#CCN(C)C(C(C(O)=O)P(O)(O)=O)C(O)=O MHDLIUDYLQIASP-UHFFFAOYSA-N 0.000 description 1
- UYNMOESGNTXLRG-UHFFFAOYSA-N 2-imidazol-1-yl-3-phosphonobutanedioic acid Chemical compound OC(=O)C(P(O)(O)=O)C(C(=O)O)N1C=CN=C1 UYNMOESGNTXLRG-UHFFFAOYSA-N 0.000 description 1
- OTANEWZGUXABLJ-UHFFFAOYSA-N 2-phosphono-3-(2-pyridin-3-ylpropan-2-yl)butanedioic acid Chemical compound OC(=O)C(P(O)(O)=O)C(C(O)=O)C(C)(C)C1=CC=CN=C1 OTANEWZGUXABLJ-UHFFFAOYSA-N 0.000 description 1
- XQFHZWGVCRSZDF-UHFFFAOYSA-N 2-phosphono-3-(pyrrolidin-1-ylmethyl)butanedioic acid Chemical compound OC(=O)C(P(O)(O)=O)C(C(=O)O)CN1CCCC1 XQFHZWGVCRSZDF-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/5532—Seven-(or more) membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Priority Applications (24)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4141928A DE4141928A1 (de) | 1991-12-19 | 1991-12-19 | Neue phosphonobernsteinsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| TW081109635A TW222636B (fr) | 1991-12-19 | 1992-12-01 | |
| IL104090A IL104090A (en) | 1991-12-19 | 1992-12-14 | Phosphonosuccinic acid derivatives, processes for the preparation thereof and pharmaceutical compositions containing these compounds |
| RU94030812A RU2115656C1 (ru) | 1991-12-19 | 1992-12-14 | Производные фосфонянтарной кислоты и их фармакологически приемлемые соли и композиция на их основе |
| EP93900042A EP0618920B1 (fr) | 1991-12-19 | 1992-12-14 | Nouveaux derives de l'acide phosphonosuccinique, leur procede de fabrication et medicaments renfermant ces composes |
| ES93900042T ES2093399T3 (es) | 1991-12-19 | 1992-12-14 | Nuevos derivados de acido fosfono-succinico, procedimiento para su preparacion y medicamentos que contienen estos compuestos. |
| PCT/EP1992/002890 WO1993012122A1 (fr) | 1991-12-19 | 1992-12-14 | Nouveaux derives de l'acide phosphonosuccinique, leur procede de fabrication et medicaments renfermant ces composes |
| AU31580/93A AU662790B2 (en) | 1991-12-19 | 1992-12-14 | Novel phosphono-succinic acid derivatives, process for producing them and medicaments containing these compounds |
| US08/244,245 US5538957A (en) | 1991-12-19 | 1992-12-14 | Phosphonosuccinic acid derivatives, processes for their preparation and medicaments containing these compounds |
| CZ941518A CZ151894A3 (en) | 1991-12-19 | 1992-12-14 | Derivatives of phosphonosuccinic acid, process of their preparation and pharmaceutical compositions containing thereof |
| HU9401834A HUT66771A (en) | 1991-12-19 | 1992-12-14 | New phosphono-succinic acid derivatives, process for producing them and medicaments containing these compounds |
| DK93900042.8T DK0618920T3 (da) | 1991-12-19 | 1992-12-14 | Hidtil ukendte phosphonravsyrederivater, fremgangsmåde til fremstilling heraf samt lægemidler indeholdende disse forbindelser |
| NZ246152A NZ246152A (en) | 1991-12-19 | 1992-12-14 | 3-(aminoalkyl- and azaheterocyclylalkyl)-2-phosphonosuccinic acid derivatives and pharmaceutical compositions |
| AT93900042T ATE141277T1 (de) | 1991-12-19 | 1992-12-14 | Neue phosphonobernsteinsäurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| CA002125867A CA2125867A1 (fr) | 1991-12-19 | 1992-12-14 | Derives d'acide phosphonosuccinique, methode de preparation et medicaments en contenant |
| JP5510624A JPH07507046A (ja) | 1991-12-19 | 1992-12-14 | 新規なホスホノコハク酸誘導体，それらの製造方法及びこれら化合物を含有する医薬品 |
| DE59206925T DE59206925D1 (de) | 1991-12-19 | 1992-12-14 | Neue phosphonobernsteinsäurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| SK746-94A SK74694A3 (en) | 1991-12-19 | 1992-12-14 | Phosphono-succinic acid derivatives, process of their production and pharmaceutical compounds on their base |
| MX9207335A MX9207335A (es) | 1991-12-19 | 1992-12-16 | Nuevos derivados del acido fosfonosuccinico, procesos para su preparacion y composicion farmaceuticas que los contiene. |
| ZA929815A ZA929815B (en) | 1991-12-19 | 1992-12-18 | New phosphonosuccinic acid derivatives processes for the preparation thereof and pharmaceutical compositions containing these compounds |
| FI942910A FI942910A0 (fi) | 1991-12-19 | 1994-06-17 | Uusia fosfonimeripihkahappojohdannaisia, menetelmä niiden valmistamiseksi ja näitä yhdisteitä sisältäviä lääkkeitä |
| NO942304A NO300546B1 (no) | 1991-12-19 | 1994-06-17 | Nye fosfonoravsyrederivater samt legemiddel inneholdende derivatene |
| US08/465,360 US5627170A (en) | 1991-12-19 | 1995-06-05 | Phosphonic acid compound containing heterocyclic substituents, pharmaceutical composition contains same and a method of treating calcium metabolism disturbance |
| GR960402474T GR3021110T3 (en) | 1991-12-19 | 1996-09-19 | Novel phosphono-succinic acid derivatives, process for producing them and medicaments containing these compounds. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4141928A DE4141928A1 (de) | 1991-12-19 | 1991-12-19 | Neue phosphonobernsteinsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE4141928A1 true DE4141928A1 (de) | 1993-06-24 |
Family
ID=6447460
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE4141928A Withdrawn DE4141928A1 (de) | 1991-12-19 | 1991-12-19 | Neue phosphonobernsteinsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| DE59206925T Expired - Fee Related DE59206925D1 (de) | 1991-12-19 | 1992-12-14 | Neue phosphonobernsteinsäurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE59206925T Expired - Fee Related DE59206925D1 (de) | 1991-12-19 | 1992-12-14 | Neue phosphonobernsteinsäurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US5538957A (fr) |
| EP (1) | EP0618920B1 (fr) |
| JP (1) | JPH07507046A (fr) |
| AT (1) | ATE141277T1 (fr) |
| AU (1) | AU662790B2 (fr) |
| CA (1) | CA2125867A1 (fr) |
| CZ (1) | CZ151894A3 (fr) |
| DE (2) | DE4141928A1 (fr) |
| DK (1) | DK0618920T3 (fr) |
| ES (1) | ES2093399T3 (fr) |
| FI (1) | FI942910A0 (fr) |
| GR (1) | GR3021110T3 (fr) |
| HU (1) | HUT66771A (fr) |
| IL (1) | IL104090A (fr) |
| MX (1) | MX9207335A (fr) |
| NO (1) | NO300546B1 (fr) |
| NZ (1) | NZ246152A (fr) |
| RU (1) | RU2115656C1 (fr) |
| SK (1) | SK74694A3 (fr) |
| TW (1) | TW222636B (fr) |
| WO (1) | WO1993012122A1 (fr) |
| ZA (1) | ZA929815B (fr) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5760021A (en) * | 1992-05-29 | 1998-06-02 | The Procter & Gamble Company | Phosphonocarboxylate compounds pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism |
| DE4320223A1 (de) * | 1993-06-18 | 1994-12-22 | Boehringer Mannheim Gmbh | Neue Phosphonobernsteinsäurederivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel |
| DE4336099A1 (de) * | 1993-10-22 | 1995-04-27 | Boehringer Mannheim Gmbh | Neue 2.4-Diphosphonoglutarsäurederivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel |
| DE4410601A1 (de) * | 1994-03-26 | 1995-09-28 | Boehringer Mannheim Gmbh | Neue 2.4-Diphosphonoglutarsäurederivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel |
| US6011021A (en) * | 1996-06-17 | 2000-01-04 | Guilford Pharmaceuticals Inc. | Methods of cancer treatment using naaladase inhibitors |
| GB2313126A (en) * | 1996-05-14 | 1997-11-19 | Albright & Wilson Uk Ltd | Polymer compositions containing phosphorus |
| US5795877A (en) * | 1996-12-31 | 1998-08-18 | Guilford Pharmaceuticals Inc. | Inhibitors of NAALADase enzyme activity |
| US5902817A (en) * | 1997-04-09 | 1999-05-11 | Guilford Pharmaceuticals Inc. | Certain sulfoxide and sulfone derivatives |
| US5863536A (en) * | 1996-12-31 | 1999-01-26 | Guilford Pharmaceuticals Inc. | Phosphoramidate derivatives |
| US6054444A (en) | 1997-04-24 | 2000-04-25 | Guilford Pharmaceuticals Inc. | Phosphonic acid derivatives |
| US6025344A (en) * | 1996-06-17 | 2000-02-15 | Guilford Pharmaceuticals Inc. | Certain dioic acid derivatives useful as NAALADase inhibitors |
| US5977090A (en) * | 1996-09-27 | 1999-11-02 | Guilford Pharmaceuticals Inc. | Pharmaceutical compositions and methods of treating compulsive disorders using NAALADase inhibitors |
| US6384022B1 (en) | 1996-06-17 | 2002-05-07 | Guilford Pharmaceuticals Inc. | Prodrugs of NAALAdase inhibitors |
| US6046180A (en) * | 1996-06-17 | 2000-04-04 | Guilford Pharmaceuticals Inc. | NAALADase inhibitors |
| US6025345A (en) * | 1996-06-17 | 2000-02-15 | Guilford Pharmaceuticals Inc. | Inhibitors of NAALADase enzyme activity |
| US6071965A (en) * | 1996-06-17 | 2000-06-06 | Guilford Pharmaceuticals Inc. | Phosphinic alkanoic acid derivatives |
| TR199802638T2 (xx) | 1996-06-17 | 1999-03-22 | Guilford Pharmaceuticals, Inc. | Kanser tedavisinde naaladase inhibit�rleri kullan�m�. |
| US5672592A (en) * | 1996-06-17 | 1997-09-30 | Guilford Pharmaceuticals Inc. | Certain phosphonomethyl-pentanedioic acid derivatives thereof |
| US5962521A (en) | 1997-04-04 | 1999-10-05 | Guilford Pharmaceuticals Inc. | Hydroxamic acid derivatives |
| US5981209A (en) * | 1997-12-04 | 1999-11-09 | Guilford Pharmaceuticals Inc. | Use of NAALADase activity to identify prostate cancer and benign prostatic hyperplasia |
| US6028216A (en) * | 1997-12-31 | 2000-02-22 | Guilford Pharmaceuticals Inc. | Asymmetric syntheses and intermediates for preparing enantiomer-enriched hydroxyphosphinyl derivatives |
| US6121252A (en) * | 1998-03-30 | 2000-09-19 | Guilford Pharmaceuticals Inc. | Phosphinic acid derivatives |
| CZ200113A3 (cs) | 1998-07-06 | 2001-08-15 | Guilford Pharmaceuticals Inc. | Inhibitory NAALAdázy využitelné jako léčiva a farmaceutické kompozice, které je obsahují |
| US6395718B1 (en) | 1998-07-06 | 2002-05-28 | Guilford Pharmaceuticals Inc. | Pharmaceutical compositions and methods of inhibiting angiogenesis using naaladase inhibitors |
| US6265609B1 (en) | 1998-07-06 | 2001-07-24 | Guilford Pharmaceuticals Inc. | Thio-substituted pentanedioic acid derivatives |
| IT1303672B1 (it) | 1998-07-28 | 2001-02-23 | Nicox Sa | Sali nitrati di farmaci attivi nei disordini ossei |
| US6313159B1 (en) | 1999-08-20 | 2001-11-06 | Guilford Pharmaceuticals Inc. | Metabotropic glutamate receptor ligand derivatives as naaladase inhibitors |
| AU2002230579A1 (en) * | 2000-10-25 | 2002-05-06 | Smithkline Beecham Corp | Calcilytic compounds |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2360797C2 (de) * | 1973-12-06 | 1985-05-23 | Henkel KGaA, 4000 Düsseldorf | Pharmazeutische Präparate |
| IL77243A (en) * | 1984-12-21 | 1996-11-14 | Procter & Gamble | Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compounds |
| US5004549A (en) * | 1989-10-10 | 1991-04-02 | Olin Corporation | Method for inhibiting scale formation using calcium hypochlorite compositions |
-
1991
- 1991-12-19 DE DE4141928A patent/DE4141928A1/de not_active Withdrawn
-
1992
- 1992-12-01 TW TW081109635A patent/TW222636B/zh active
- 1992-12-14 DE DE59206925T patent/DE59206925D1/de not_active Expired - Fee Related
- 1992-12-14 CZ CZ941518A patent/CZ151894A3/cs unknown
- 1992-12-14 CA CA002125867A patent/CA2125867A1/fr not_active Abandoned
- 1992-12-14 EP EP93900042A patent/EP0618920B1/fr not_active Expired - Lifetime
- 1992-12-14 RU RU94030812A patent/RU2115656C1/ru active
- 1992-12-14 DK DK93900042.8T patent/DK0618920T3/da active
- 1992-12-14 AU AU31580/93A patent/AU662790B2/en not_active Ceased
- 1992-12-14 US US08/244,245 patent/US5538957A/en not_active Expired - Fee Related
- 1992-12-14 NZ NZ246152A patent/NZ246152A/en unknown
- 1992-12-14 ES ES93900042T patent/ES2093399T3/es not_active Expired - Lifetime
- 1992-12-14 JP JP5510624A patent/JPH07507046A/ja active Pending
- 1992-12-14 IL IL104090A patent/IL104090A/xx not_active IP Right Cessation
- 1992-12-14 HU HU9401834A patent/HUT66771A/hu unknown
- 1992-12-14 SK SK746-94A patent/SK74694A3/sk unknown
- 1992-12-14 AT AT93900042T patent/ATE141277T1/de active
- 1992-12-14 WO PCT/EP1992/002890 patent/WO1993012122A1/fr not_active Application Discontinuation
- 1992-12-16 MX MX9207335A patent/MX9207335A/es not_active IP Right Cessation
- 1992-12-18 ZA ZA929815A patent/ZA929815B/xx unknown
-
1994
- 1994-06-17 NO NO942304A patent/NO300546B1/no not_active IP Right Cessation
- 1994-06-17 FI FI942910A patent/FI942910A0/fi unknown
-
1995
- 1995-06-05 US US08/465,360 patent/US5627170A/en not_active Expired - Fee Related
-
1996
- 1996-09-19 GR GR960402474T patent/GR3021110T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL104090A0 (en) | 1993-05-13 |
| EP0618920B1 (fr) | 1996-08-14 |
| CA2125867A1 (fr) | 1993-06-24 |
| ATE141277T1 (de) | 1996-08-15 |
| NZ246152A (en) | 1995-12-21 |
| IL104090A (en) | 1997-03-18 |
| NO942304L (fr) | 1994-08-16 |
| ES2093399T3 (es) | 1996-12-16 |
| FI942910A (fi) | 1994-06-17 |
| TW222636B (fr) | 1994-04-21 |
| WO1993012122A1 (fr) | 1993-06-24 |
| EP0618920A1 (fr) | 1994-10-12 |
| US5627170A (en) | 1997-05-06 |
| HUT66771A (en) | 1994-12-28 |
| US5538957A (en) | 1996-07-23 |
| DK0618920T3 (da) | 1996-12-30 |
| AU3158093A (en) | 1993-07-19 |
| RU2115656C1 (ru) | 1998-07-20 |
| FI942910A0 (fi) | 1994-06-17 |
| HU9401834D0 (en) | 1994-09-28 |
| AU662790B2 (en) | 1995-09-14 |
| NO942304D0 (no) | 1994-06-17 |
| ZA929815B (en) | 1994-06-20 |
| SK74694A3 (en) | 1995-02-08 |
| CZ151894A3 (en) | 1995-01-18 |
| GR3021110T3 (en) | 1996-12-31 |
| NO300546B1 (no) | 1997-06-16 |
| DE59206925D1 (de) | 1996-09-19 |
| MX9207335A (es) | 1993-06-01 |
| JPH07507046A (ja) | 1995-08-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8139 | Disposal/non-payment of the annual fee |